tbuckley/cabot-search huggingface dataset:
Real-world treatment patterns in patients with Sézary syndrome in the United States and the impact of Covid-19.
Authors: Yang Zhao, Jackson Tang, Huanxue Zhou, Takeshi Takahashi, Takanobu Nomura, Eslie Dennis, Oleg Akilov
Journal: Journal of Clinical Oncology (2022)

e19578 Background: Sézary syndrome (SS) is an aggressive type of cutaneous T-cell lymphomas (CTCL). Due to its low prevalence, there are limited data on real-world treatment patterns of currently available SS therapies. Furthermore, recent approvals of new agents for patients with CTCL as well as COVID-19 likely impacted real-world treatment patterns. Objective: To examine real-world treatment patterns and the impact of COVID-19 among SS patients treated in 2018-2020 in the US. Methods: Patients with public or private insurance in the 2018-2020 Symphony Health Solutions database were classified into 3 groups: ≥1 diagnosis of SS (ICD-10-CM code: C84.1x) in 2018, 2019, and 2020, respectively. Patient characteristics and treatment patterns for all therapies recommended by the National Comprehensive Cancer Network guidelines version 2.2021 were examined: systemic therapy (e.g., extracorporeal photopheresis (ECP), parenteral, or oral agents), skin-directed therapy (SDT, e.g., topical, local radiation, total skin electron beam therapy, or phototherapy) and bone marrow transplant. The impact of COVID-19 was assessed via quarterly analysis. National drug codes, current procedural terminology and healthcare common procedure coding system codes were used to identify all treatments. Results: The analyses included 869, 882, and 853 SS patients in 2018, 2019, and 2020, respectively (mean age: 66.3, 66.9 and 67.3 years; male: 54.4%, 54.8%, and 55.6%). Overall, systemic therapy increased from 2018 to 2020 (41.8% to 46.5%), with increased parenteral (20.7% to 28.7%) but decreased ECP (17.0% to 13.5%) usage. SDT increased from 2018 to 2020 (48.9% to 52.9%), with increased topical (42.3% to 48.3%) but decreased phototherapy (6.3% to 4.1%) usage. ECP, mogamulizumab, and bexarotene were the most prescribed systemic therapies in 2019-2020, with mogamulizumab being the only one with increased usage over time. Quarterly analysis showed a decreasing ECP from Q1 to Q4 within each year, with a notable drop in Q2 2020. For parental systemics, there was an increasing trend in 2019 and 2020, but utilization in Q4 2020 was lower than that of Q3 2020. For oral systemic, there was a notable drop in Q2 2020 but an increased trend in Q3-Q4 2020. Conclusions: This claims analysis indicated increased use in systemic and SDT among SS patients in 2018-2020. The quarterly analysis indicated that the drop in ECP and oral systemic usage in Q2 2020 coincided with the onset of the pandemic, but there was a stable use of parenteral systemic during 2020.
QOL-15. Life happens wherever you are! Use of Avatar AV1 to enhance Health-Related Quality of Life, Sense of Belonging and Social Inclusion in Children and Adolescents with Chronic Illnesses
Authors: Thomas Pletschko, Clarissa Pelzer, Martin Röhsner, Gerda Rockenbauer, Agnes Turner
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Due to regular hospital check-ups, inpatient treatments, or a weakened immune system, children with brain tumors experience frequent and long absences from school and social activities. Returning to school presents a challenge for these patients, as they experience reduced health-related quality of life (HRQOL), decreased sense of belonging and a lack of social inclusion in class. To prevent social and emotional problems, telepresence systems such as the Avatar AV1 are described as promising approach for pediatric patients. OBJECTIVES: To sustainably improve social inclusion in times of illness-related absence for these patients, the first study in Austria investigating effects of the use of the Avatar is pursuing both, a qualitative and quantitative approach. METHODS: To examine effects on social inclusion, sense of belonging and HRQOL in pediatric patients, interviews were conducted with patients, their parents, teachers and classmates within the qualitative approach and questionnaires were administered at three times (before -, after 6 months Avatar-use and 3 months after returning the Avatar) within the quantitative approach. The sample consists of pediatric patients (6 to 18 years). RESULTS: Categories from n=24 interviews indicate that a positive attitude towards and identification with the Avatar as well as the patients’ psychological condition and social inclusion into class before the illness play major roles. Preliminary findings from the ongoing longitudinal quantitative survey indicate that the Avatar has significant positive and stabilizing effects on HRQOL, sense of belonging and social inclusion of pediatric patients. CONCLUSION: This study is the first to describe the impact of Avatar use on social inclusion in children with brain tumors. To strengthen the sense of belonging in these children, the pedagogical-interactional component needs to be brought in focus. Through pedagogical-didactical adaptions, a routine handling of and a positive attitude towards the telepresence system, pediatric patients highly benefit from the Avatar.
Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome
Authors: Julian A. Villalba, Caroline F. Hilburn, Michelle A. Garlin, Grant A. Elliott, Yijia Li, Keiko Kunitoki, Sergio Poli, George A. Alba, Emilio Madrigal, Manuel Taso, Melissa C. Price, Alexis J. Aviles, Milagros Araujo-Medina, Liana Bonanno, Baris Boyraz, Samantha N. Champion, Cynthia K. Harris, Timothy L. Helland, Bailey Hutchison, Soma Jobbagy, Michael S. Marshall, Daniel J. Shepherd, Jaimie L. Barth, Yin P. Hung, Amy Ly, Lida P. Hariri, Sarah E. Turbett, Virginia M. Pierce, John A. Branda, Eric S. Rosenberg, Javier Mendez-Pena, Ivan Chebib, Ivy A. Rosales, Rex N. Smith, Miles A. Miller, Ivan O. Rosas, Charles C. Hardin, Lindsey R. Baden, Benjamin D. Medoff, Robert B. Colvin, Brent P. Little, James R. Stone, Mari Mino-Kenudson, Angela R. Shih
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: The leading cause of death in coronavirus disease 2019 (COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective: To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods: This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia (n = 20) and with respiratory failure and histologic DAD (n = 21; non-COVID-19 viral and nonviral etiologies). Premortem chest computed tomography (CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion (CVasc) in different microscopic compartments. Respiratory mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results: In premortem CT, patients with COVID-19 showed more dilated vasculature when all lung segments were evaluated (P = 0.001) compared with controls with DAD. Histopathology revealed vasculopathic changes, including hemangiomatosis-like changes (P = 0.043), thromboemboli (P = 0.0038), pulmonary infarcts (P = 0.047), and perivascular inflammation (P < 0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc range (P = 0.002). Alveolar-septal congestion was associated with a significantly shorter time to death from symptom onset (P = 0.03), length of hospital stay (P = 0.02), and increased ventilatory ratio [an estimate for pulmonary dead space fraction (Vd); p = 0.043] in all cases of ARDS. Conclusions: Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.
Immune landscape of colorectal cancer lung metastasis.
Authors: Song-Yi Lee, Minae An, Jeeyun Lee
Journal: Journal of Clinical Oncology (2022)

e15542 Background: Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death worldwide. What makes CRC treatment a challenge is synchronous or metachronous recurrence at distant organs; metastasis. Approximately half of CRC patients develop metastases in the course of the disease and the most prevalent metastatic site is liver, followed by lung and peritoneum. A 5-year survival rate metastatic CRC is much poorer than that of patients with regional and localized CRC. Methods: From 2019 to 2020, 9 metastatic CRC patients who had recurrence to lung oligo-metastases were enrolled. These patients were eligible for lung metastatectomy of curative intent. The surgically resected lung metastases were collected and whole exome sequencing/RNA sequencing,10x chromium single cell RNA sequencing analysis were performed. The purpose of this study was to uncover distinctive tumor microrenvironment (TME) of the lung metastases from CRC, we compared these results with those from public available primary CRC data. Results: We successfully analyzed all 9 metastatic lung samples. Compared to primary CRC, we found that lung metastasis had more immune-suppressive TMEs, represented by downregulation of TCR signaling, innate/adaptive immune system and antigen presentation. In addition, there were higher expression levels of immune checkpoint molecules, such as PD-1, LAG-3 and TIGIT in metastatic lung samples when compared to primary colon cancer public database. Macrophage polarization of lung metastases toward alternatively activated M2 subset, rather than classically activated M1 subset, resulting in low M1/M2 ratio, was also thought to attribute to immune suppressive environments of the lung metastases and successful colonization of primary tumors. Conclusions: This study identified different TMEs of lung metastasis specimens from primary CRCs. Our study underscores the importance of the tumor microenvironment and the anatomic location of the tumor cells for optimized immunotherapeutic strategies.
Efficacy and prognosis of sequential 2G ALK-TKI in ALK-positive advanced NSCLC after crizotinib resistance: A real-world single-center research.
Authors: Liyuan He, Jing Zuo, Li Feng, Zhisong Fan, Long Wang, Xinliang Zhou, Jing Han, Xue Zhang, Jiayin Liu, Dan Li, Feiran Liu, Honghui Zhao, Yudong Wang
Journal: Journal of Clinical Oncology (2022)

e21075 Background: Advanced-stage anaplastic lymphoma kinase fusion-positive (ALK[+]) NSCLC has significantly benefited from ALK-TKI. It is still uncertain which second-generation(2G) ALK-TKI will benefit patients more after crizotinib resistance. Methods: We retrospectively analyzed the treatment history of 104 patients with ALK[+] NSCLC. Grouping was determined according to the type of 2G TKI patients selected after failure of crizotinib, including systemic and intracranial. Results: Overall, the median follow-up time was 24.2 (95%CI: 21.3-27.1) months, and 45(43.2%) eligible patients were alive at the end of follow-up. After Crizotinib treatment failure, 91(87.5%) patients received subsequent therapy (including targeted therapy and chemotherapy), and 90.1% (82/91) of patients received sequential 2G TKI treatment, with overall ORR of 68.3%, mPFS of 13.4 (95%CI:10.0-16.7) months, and mOS of 26.3 (95%CI:11.6-41.1) months. The mOS for Alectinib, Ceritinib, and Brigatinib were 34.5 (95%CI: 14.8-54.3), 19.4 (95%CI: 11.8-27.0) and 43.8 (95%CI: 10.0-77.6) months, respectively. The mPFS of Alectinib, Ceritinib, Brigatinib and Ensartinib were 17.3 (95%CI: 12.9-21.8) months, 13.4 (95%CI: 9.5-17.8) months, 10.7 (95%CI: 6.6-14.9) months and 8.4 (95%CI: 1.3-14.8) months, ORR were 68.6%, 70.8%, 69.2% and 60.0%, respectively (Table.1). For crizotinib resistant patient, 2G TKI showed no significant difference in prolonging PFS (P = 0.599) and OS (P = 0.681). Brain metastases were found in 67.1% (55/82) of crizotinib resistant patients, and mPFS of Alectinib, Ceritinib, Brigatinib and Ensartinib were 22.1 (95%CI:9.6-30.6) months, 12.6 (95%CI:8.3-16.9) months, 21.0 (95%CI:0.5-45.7) months and 14.7 (95%CI:3.8-25.5) months; ORR were 72.4%, 50.0%, 66.7% and 40.0%, respectively (Table.1). In particular, the ORR of Alectinib and Brigatinib was significantly higher than that of Ceritinib and Ensartinib (P &lt; 0.000), while the mPFS of Alectinib was significantly better than Ensartinib (P = 0.029). Conclusions: After crizotinib resistance, nearly 90% of patients choose sequential 2G TKI. There was no significant difference in mPFS and mOS among patients treated with different 2G ALK-TKI. For patients with CNS metastases, treatment with Alectinib and Brigatinib results in higher ORR and PFS.[Table: see text]
Association of Maternal Use of Triptans During Pregnancy With Risk of Attention-Deficit/Hyperactivity Disorder in Offspring
Authors: Gerd Marie Harris, Mollie Wood, Eivind Ystrom, Hedvig Nordeng
Journal: JAMA Network Open (2022)

Triptans are commonly used in the treatment of migraine. Prenatal exposure to triptans may be associated with adverse fetal neurodevelopment; however, there is limited information about the long-term safety of triptan use during pregnancy.To examine the association between maternal use of triptans during pregnancy and diagnosis and symptoms of attention-deficit/hyperactivity disorder (ADHD) among offspring.This study used data from the Norwegian Mother, Father and Child Cohort Study (recruitment 1999-2008), linked to national health registries. Live-born singleton children born to women with migraine before or during pregnancy were included. Two analytic samples were defined: one to assess ADHD diagnosis and one to assess ADHD symptoms. Data were analyzed from May 1 to November 30, 2021.Maternal self-report of triptan use during pregnancy. Exposed children were compared with 2 groups of unexposed children whose mothers reported migraine (1) during pregnancy and (2) before pregnancy only.An ADHD diagnosis was defined as diagnosis of hyperkinetic disorder or receipt of dispensed ADHD medication. Symptoms of ADHD at 5 years were measured by the Conners' Parent Rating Scale, where a higher score indicates more symptoms of ADHD. Cox proportional hazards regression models and generalized linear models with inverse probability weights were used to estimate weighted hazard ratios (HRs) and standardized mean differences, respectively, with 95% CIs.The ADHD diagnosis sample comprised 10 167 children (mean [SD] maternal age, 30.2 [4.6] years; 5231 boys [51.5%]), and the ADHD symptoms sample comprised 4367 children (mean [SD] maternal age, 30.6 [4.4] years; 2191 boys [50.2%]). Children were followed up for a mean (SD) of 10.6 (2.2) years. Children with prenatal triptan exposure had no increased risk of ADHD diagnosis compared with unexposed children whose mothers had migraine during pregnancy (weighted HR, 1.16; 95% CI, 0.78-1.74) and compared with unexposed children whose mothers had migraine only before pregnancy (weighted HR, 1.28; 95% CI, 0.84-1.94). There were no differences in ADHD symptom scores between exposed and unexposed children.The findings of this study suggest that there is no increased risk of ADHD among offspring associated with prenatal exposure to triptans.
Subtype specific expression of radioligand targets in the prospective Real World clinico-pathological register trial BRIDGister
Authors: R. Wirtz, F. Friedersdorff, D. Barski, T. Otto, R. Bug, E. Veltrup, E. Kilic, R. Hake, S. Eidt, M. Waldner, P. Grabowski, M. Pavel, J. Roggisch, S. Koch, A. Heidenreich, R.P. Baum, T.H. Ecke
Journal: European Urology (2022)
Cortisol regulates adrenaline synthesis via phenylethanolamine N-methyltransferase in surgical specimens of pheochromocytoma
Authors: K. Numakura, Y. Sekine, Y. Muto, M. Kobayashi, S. Kashima, R. Yamamoto, A. Koizumi, T. Nara, M. Saito, S. Narita, T. Habuchi
Journal: European Urology (2022)
Assessment of a 4-chemokine signature in prediction of T-cell inflammation and response to immune checkpoint inhibition across tumor types.
Authors: Joan Miguel Romero, Emma Titmuss, Yifan Wang, James Vafiadis, Alain Pacis, Gun Ho Jang, Amy Zhang, Bryn Golesworthy, Tatiana Lenko, Laura Williamson, Barbara Grunwald, Grainne M. O'Kane, Julie Wilson, Steven Gallinger, Janessa J. Laskin, George Zogopoulos
Journal: Journal of Clinical Oncology (2022)

2558 Background: Immune checkpoint inhibitors (ICI) are highly effective in select cancers. Novel predictors of T cell-inflammation may identify a broader subset of tumors with ICI responsiveness. Our group has identified four chemokines (CCL4, CCL5, CXCL9, CXLC10) able to predict a T cell-inflamed phenotype in primary and metastatic pancreatic tumors. Here, we test whether this 4-chemokine signature can predict T cell-inflammation across additional tumor types and response to ICI. Methods: Using matched genomic and transcriptomic data from 6,455 patients spanning 25 tumor types from The Cancer Genome Atlas, we searched for associations between the 4-chemokine signature and metrics of antitumor immunity. Further, we tested the association of this signature with markers of DNA damage repair deficiency. We also investigated the ability of this signature to predict response to immunotherapy using real-world data from a pan-cancer cohort of 82 patients in the Personalized OncoGenomics Program who had received ICI. Results: The majority of tumor types displayed sub-populations with high expression of the 4-chemokines (4-chemokine hi ) and transcriptional hallmarks of the cancer-immunity cycle. Testicular germ cell tumors, cervical squamous cell carcinomas, and head and neck squamous cell carcinomas were the strongest expressors of the signature. Immunomodulatory genes, including PD-L1, PD-1, TIM3, LAG3, TIGIT, CTLA-4, and FASLG, were significantly overexpressed (p&lt;0.05) in the 4-chemokine hi cohorts. Genesets of processes involved in the cancer-immunity cycle, including MHC I expression and cytolytic activity, were upregulated in the 4-chemokine hi cohorts (p&lt;0.05). While a global relationship between tumor mutation burden (TMB) and 4-chemokine expression across tumor histological type was seen (rho=0.42, p=0.02), high TMB was associated with only a subset of 4-chemokine hi tumors. Among patients treated with ICIs, those with 4-chemokine hi tumors had a longer median time to progression (104 versus 71 days, p=0.013) and overall survival (391 versus 195 days, p=0.016). The 4-chemokine signature outperformed TMB for overall survival prediction. Conclusions: Sub-populations of T cell-inflamed patients exist across tumor types and may therefore respond favourably to ICI. The 4-chemokine signature has the potential to select a wider spectrum of patients that may benefit from ICIs. [Table: see text]
Diagnosing prostate cancer in asymptomatic patients
Authors: Stephen H Bradley, Garth Funston, Daniel Jones, Jessica Watson
Journal: BMJ (2022)

The pandemic has disrupted the diagnosis and treatment of cancer in health systems worldwide.In response, patients at risk of cancer have been encouraged to present to health services to support prompt diagnosis. 1 In England, this has included a collaboration between the NHS and Prostate Cancer UK to find the 14 000 men estimated to have not yet started treatment for prostate cancer because of the pandemic.
Survival outcomes in patients with chronic lymphocytic leukemia treated at academic centers.
Authors: Victoria Vardell, Daniel Arthur Ermann, Harsh Shah, Lindsey Fitzgerald, Boyu Hu, Deborah Marie Stephens
Journal: Journal of Clinical Oncology (2022)

7544 Background: Chronic lymphocytic leukemia (CLL), the most prevalent leukemia in western countries, is associated with highly variable clinical outcomes. This study aims to evaluate whether patients with CLL treated at Commission on Cancer accredited academic centers (ACs), which offer high clinical volume, clinical trial access, and postgraduate physician education, have improved survival compared to non-academic centers (NACs). Methods: The National Cancer Database (NCDB) was used to identify CLL patients diagnosed between 2004-2018. Demographic and treatment characteristics were compared between center categories with binary logistic regression for odds of receiving CLL treatment at an AC. Survival analysis was completed with Kaplan Meier and multivariate Cox regression, adjusted for the only available disease-related characteristics in the NCDB, age and Charlson-Deyo comorbidity score, to compare overall survival (OS). Results: Of the 98,186 patients identified, 33.3% were treated at ACs. Patients treated at ACs were younger than those treated at NACs (median age 67 vs. 71 years, p&lt;0.001). ACs were more likely to treat Black and other minority patients, with Black patients representing 9.7% vs. 6.3% of AC vs NAC patients (p&lt;0.001). ACs were more likely than NACs to treat privately insured (39.1% vs. 30.3%), uninsured (3.2% vs.2.0%) and patients on Medicaid (4.1% vs. 2.9%) (p&lt;0.001), as well as patients from the highest quartiles of income (OR 1.46), and education (OR 1.12), when referenced to lowest quartiles (p&lt;0.001). ACs were more likely to manage patients with surveillance versus NACs (53.7% vs. 45%, p&lt;0.001). With a median follow up of 4.3 years, median OS at ACs was significantly improved when compared to NACs, with a median OS of 11.0 years (CI 10.5-11.3) vs. 8.2 years (CI 8.1-8.3), respectively (p&lt;0.001). Survival benefit was maintained at both 5-years (73% vs. 66%) and 10-years (53% vs. 43%) (both p&lt;0.001). On multivariate analysis adjusted for age and comorbidity, management of CLL patients at ACs was an independent factor for improved OS (HR 0.87, CI 0.85-0.89, p&lt;0.001). Conclusions: In this study of a large population of CLL patients, there is significant demographic and socioeconomic variation between CLL patients treated at ACs and NACs. While our study is limited by the available disease and treatment level data available, the improved OS benefit of CLL patients managed at ACs suggests possible differences in treatment and clinical trial availability, and supportive care management. Further investigations into the factors contributing to such disparities would be beneficial to help standardize care and improve outcomes. [Table: see text]